内皮蛋白C受体、加强蛋白C与肺部疾病的关系

内皮蛋白C受体（EPCR）是新近分离纯化的蛋白,作为蛋白C抗凝系统中新的一员,其在加强蛋白C（APC）活化和调节炎症反应方面有着重要作用。EPCR介导的活化的PC在急性肺损伤、肺纤维化和支气管哮喘等肺部炎症性疾病中具有重要意义,是未来研究的方向之一。     

C反应蛋白与动脉粥样硬化

C反应蛋白(CRP)作为炎症介质被认为是心血管事件最强有力的预测因子之一.慢性炎症是动脉粥样硬化发生发展的重要机制.作为急性时相反应蛋白的CRP从其结构、生物特性来看与炎症反应关系密切,成为动脉粥样硬化的介导和标志物.本文就CRP与AS的关系作一综述.     

高敏C反应蛋白与动脉粥样硬化

采用超敏感方法检测到的C反应蛋白被称为高敏C反应蛋白.高敏C反应蛋白在冠心病、中风、周围血管栓塞等疾病诊断和预测中发挥越来越重要的作用.越来越多的研究揭示了C反应蛋白直接参与了炎症与动脉粥样硬化等心血管疾病,并且是心血管疾病最强有力的预示因子与危险因子之一.各种炎症、组织感染损伤均会引起循环中多种血浆蛋白水平增加,其中C反应蛋白作为一种急性期反应蛋白,其水平增高是体内炎症的敏感指标.而炎症在动脉粥样硬化及心血管相关疾病的发生和发展过程中都起着重要的作用.本文将高敏C反应蛋白和动脉粥样硬化之间的关系及其机制进行综述.     

C反应蛋白与高血压病心房颤动关系的临床研究

目的:探讨C反应蛋白作为系统炎症因子在高血压病心房颤动的发生和发展中的作用。方法:对资料完整的87例高血压病患者,高血压对照组29例,阵发性房颤组26例和永久性房颤组32例,测定并比较各组C反应蛋白水平。结果:血清C反应蛋白水平:心房颤动组比正常对照组的水平明显增高(P<0.01),永久性房颤组高于阵发性房颤组(P<0.01)。左房直径与C反应蛋白水平呈正相关(r=0.56,P<0.05)。结论:C反应蛋白在心房颤动患者中明显升高,说明炎症状态在高血压病心房颤动的发生和维持中起一定作用。     

C反应蛋白与慢性阻塞性肺疾病

C反应蛋白是在机体炎症、感染或组织损伤时,由一种肝细胞合成释放的急性时相反应蛋白.在众多慢性阻塞性肺疾病患者血清中水平增加的炎症因子中,C反应蛋白是研究最多的一种.本文重点针对C反应蛋白在慢性阻塞性肺疾病中的作用方面的进展进行阐述.     

C反应蛋白与冠心病的研究进展

近期研究显示,动脉硬化斑块不是简单的脂质沉积改变,而是一种慢性炎症反应,炎症在冠状动脉粥样硬化的发生、发展中起重要作用的结论已比较肯定[1]。C反应蛋白(CRP)是炎症反应的标志物,血清中CRP是炎症急性期的反应和非特异性的标志,它是在激活的中性粒细胞和巨核细胞产生的各种胞质分裂刺激后由肝脏细胞合成的,可用于检测心血管低度炎症状态[2]。随着高敏C反应蛋白(hs-CRP)的研究逐渐深入,越来越多的研究证明,CRP与动脉粥样硬化,冠心病(CHD)的发生、发展和预后有着密切的关系,CRP作为炎症标志物被认为对心血管事件的预测有重要的临…     

C反应蛋白与冠心病关系的研究进展

炎症在冠心病的发生、发展中起着重要的作用.c反应蛋白是一种重要的炎症因子,其与冠心病的关系近年来已逐渐成为研究热点,越来越多的研究显示它在动脉粥样硬化的形成、演变及破裂过程中起着至关重要的作用,是造成斑块不稳定、斑块破裂的重要因素,临床上检测C反应蛋白有助于冠心病的诊断和严重程度判断,对介入治疗也有指导意义.     

补体C1q/肿瘤坏死因子相关蛋白中CTRP3、CTRP5、CTRP9、CTRP13生物学研究进展

感染性和炎症性疾病常伴有代谢改变,代谢相关脂肪性肝病(MAFLD)和T2DM特点是具有高水平的促炎细胞因子.补体C1q/TNF相关蛋白(CTRPs)的APN家族因抗炎和Ins增敏作用引起关注.CTRP3、CTRP5、CTRP9、CTRP13可通过调节代谢途径、影响免疫炎症反应控制MAFLD和T2DM的发生发展.本文对C...     

细胞外硫氧还蛋白的作用

硫氧还蛋白(thioredoxin,Trx)是具有多种生物学功能的一种小分子蛋白质.它和硫氧还蛋白还原酶及NADPH组成硫氧还蛋白系统,具有抗氧化、促细胞生长、抗细胞凋亡和调节转录因子活性作用.近年研究发现,Trx可以分泌到细胞外,而胞外Trx与许多疾病有关.胞外Trx抑制中性粒细胞到炎症反应部位,抑制促炎因子的表达释放.因此,胞外Trx即可作为一些疾病的标志,同时又具有重要的免疫调节作用.     

C反应蛋白与动脉粥样硬化性心脑血管病

在动脉粥样硬化形成的炎症机制中 ,C反应蛋白 (CRP)起着重要作用。超敏CRP检测可用于评价动脉粥样硬化性心脑血管病的危险性。通过监测CRP指导抗炎治疗 ,可能会在心脑血管病的一、二级预防中发挥重要作用。     

Activated protein C and inflammation in human myocardium after heart surgery

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.     

Treatment of homozygous protein C deficiency with subcutaneous protein C concentrate

Subcutaneous protein C concentrate (Immuno, Vienna) was used to treat a child with homozygous protein C deficiency who was formerly treated with intravenous protein C concentrate. After 3000 units subcutaneous protein C concentrate (250 iu/kg), protective protein C levels were maintained for 48h after infusion, with peak levels at 12h. Subcutaneous protein C concentrate is given every third day and is well tolerated by the patient. No thrombotic events have occurred. We conclude that subcutaneous administration of protein C concentrate is a valuable therapeutic option in the long-term management of homozygous protein C deficiency and avoids the potential hazards of long-term central venous lines.     

Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation

Chronic renal failure (CRF) courses with both systemic inflammatory reaction and haemostatic activation. We explored the relationship of these processes with plasma levels of free, activated protein C (APC) and complexes of APC with its inhibitors in patients with CRF under conservative treatment. Plasma concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFalpha) and interleukin 8], acute-phase proteins (C-reactive protein, fibrinogen, alpha1-anti-trypsin and von Willebrand factor), and markers of haemostatic activation (thrombin-anti-thrombin complexes, plasmin-anti-plasmin complexes, and fibrin and fibrinogen degradation products) were higher in patients than in controls. Inflammatory and haemostatic markers were significantly and positively correlated. Total plasma APC and APC:alpha1-anti-trypsin (alpha1AT) complexes were 44% and 75% higher in patients than in controls (P = 0.0001), whereas free APC was 20% lower (P < 0.015). No significant difference was observed in APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC ratio was significantly lower in patients than in controls (P < 0.0001). Total plasma APC and APC:alpha1AT were positively correlated with activation markers of haemostasis and acute-phase proteins, whereas free APC was inversely correlated with plasma levels of creatinine, acute-phase proteins and fibrin degradation products (FnDP). Systemic inflammation and activation of haemostasis are interrelated processes in CRF. APC generation was increased in response to elevated thrombin production, but the inflammatory reaction, associated with increased synthesis of alpha1AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.     

Activated protein C action in inflammation

Activated protein C (APC) is a natural anticoagulant that plays an important role in coagulation homeostasis by inactivating the procoagulation factor Va and VIIIa. In addition to its anticoagulation functions, APC also has cytoprotective effects such as anti‐inflammatory, anti‐apoptotic, and endothelial barrier protection. Recently, a recombinant form of human APC (rhAPC or drotrecogin alfa activated; known commercially as ‘Xigris’) was approved by the US Federal Drug Administration for treatment of severe sepsis associated with a high risk of mortality. Sepsis, also known as systemic inflammatory response syndrome (SIRS) resulting from infection, is a serious medical condition in critical care patients. In sepsis, hyperactive and dysregulated inflammatory responses lead to secretion of pro‐ and anti‐inflammatory cytokines, activation and migration of leucocytes, activation of coagulation, inhibition of fibrinolysis, and increased apoptosis. Although initial hypotheses focused on antithrombotic and profibrinolytic functions of APC in sepsis, other agents with more potent anticoagulation functions were not effective in treating severe sepsis. Furthermore, APC therapy is also associated with the risk of severe bleeding in treated patients. Therefore, the cytoprotective effects, rather than the anticoagulant effect of APC are postulated to be responsible for the therapeutic benefit of APC in the treatment of severe sepsis.     

Endotoxaemia induces resistance to activated protein C in healthy humans

Systemic inflammation activates the tissue factor/factor VIIa complex (TF/FVIIa), leading to a procoagulant state, which may be enhanced by impairment of physiological anticoagulant pathways, such as the protein C system. Besides impaired protein C activation, resistance to activated protein C (APC) may occur. We studied the effect of endotoxemia on APC resistance, analysed its determinants and evaluated the effect of TF/FVIIa inhibition on endotoxin-induced APC resistance. Sixteen healthy male volunteers participated in the study, eight receiving endotoxin alone and eight receiving the combination of endotoxin and recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent inhibitor of TF/FVIIa. Parameters of coagulation were subsequently studied. The sensitivity to APC was determined by two tests: a test based on the endogenous thrombin potential and a test based on the activated partial thromboplastin time. In response to endotoxemia, both tests detected a transient APC resistance that was predominantly mediated by an increase in factor VIII and was not influenced by TF/FVIIa inhibition. In vitro tests confirmed that an increase in factor VIII induced APC resistance, as measured by both tests. This finding suggests that APC resistance might play a role in the procoagulant state occurring during human endotoxemia.     

C反应蛋白测定在肺部感染中的应用

目的　观察 C反应蛋白测定在肺部感染中的临床应用价值。方法　通过检测肺部感染患者治疗前和治疗后的血清 C反应蛋白 (CRP)浓度、血白细胞总数 (WBC)、中性粒细胞百分比 (N)、血沉 (ESR)以及痰培养 ,进行统计学比较。结果　入院时 CRP均 >10 mg/ L ,治疗后的 CRP水平明显降低 (p<0 .0 1) ,且 CRP的阳性率明显高于 ESR、WBC、N和痰培养。结论　 CRP可作为诊断肺部感染和观察治疗效果的敏感指标     

Decreased protein C activation in patients with fulminant hepatic failure

Objective. Abnormalities of the blood coagulation system have an influence on outcome in patients with fulminant hepatic failure (FHF). The protein C (PC) pathway is one of the main modulators of the blood coagulation system. The role of the PC pathway in FHF is not clear. In the present study, we evaluated endothelial cell injury and the grade of activated protein C (APC) generation in FHF patients. Material and methods. The effect of APC on the expression of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 from LI90 stellate cells was also evaluated. This study comprised 5 patients with FHF, 6 with acute hepatitis (AH), 12 with chronic hepatitis (CH) and 20 healthy subjects. Results. The plasma concentrations of thrombin-antithrombin complex and thrombomodulin were significantly increased in FHF patients compared with those in AH patients and healthy subjects. The circulating levels of activated protein C-protein C inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were significantly decreased in patients with FHF compared to healthy controls. APC significantly inhibited in vitro the expression of TNFα and MCP-1 from LI90 stellate cells. Conclusions. This study demonstrated enhanced endothelial cell injury in association with decreased PC activation and hypercoagulability in FHF.     

丝裂原活化蛋白激酶激活的蛋白激酶2在心血管系统中的作用

心血管疾病的发生发展与慢性炎症有关。p38丝裂原活化蛋白激酶(MAPK)介导的信号通路在心血管细胞炎症、增殖、分化、迁移和代谢中起着重要作用。抑制p38MAPK可有效抑制炎症介质的表达,由于p38抑制剂在安全性方面不可接受,故研究其下游底物是很有必要的。丝裂原活化蛋白激酶激活的蛋白激酶2(MK2)是p38MAPK重要的下游底物且参与了心血管疾病的发生发展。因此抑制MK2的活性在心血管疾病的治疗及预防中具有重大的临床意义。文章主要对MK2的结构功能和在心血管疾病中的作用展开综述。